Submissions for variant NM_033305.3(VPS13A):c.3961-2A>C

gnomAD frequency: 0.00004  dbSNP: rs1244139989

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001204165	SCV001375359	likely pathogenic	not provided	2024-01-31	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 34 of the VPS13A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in VPS13A are known to be pathogenic (PMID: 12404112, 21598378). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with VPS13A-related conditions. ClinVar contains an entry for this variant (Variation ID: 935544). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Natera, Inc.	RCV001828638	SCV002078251	likely pathogenic	Chorea-acanthocytosis	2020-08-16	no assertion criteria provided	clinical testing